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Clinical and Translational Research

One-Year Experience With High-Emergency Lung Transplantation in France

Boussaud, Véronique1; Mal, Hervé2,12; Trinquart, Ludovic3; Thabut, Gabriel2; Danner-Boucher, Isabelle4; Dromer, Claire5; Raymond, Christelle Saint6; Reynaud-Gaubert, Martine7; Kessler, Romain8; Philit, François9; Dorent, Richard10; Stern, Marc11

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doi: 10.1097/TP.0b013e31824d7079
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Almost 30 years after the first clinical success with lung transplantation (LTx), the procedure has become a valid option for treating advanced respiratory diseases in selected patients (1–3). One of the main problems LTx teams face is the significant number of patients accepted for LTx who die while on the waiting list (4). These deaths result from a mismatch between supply and demand, with the number of candidates for LTx far exceeding the number of lungs available.

In addition to strategies for increasing the number of available lungs, the implementation of an urgency-based lung allocation policy can increase the survival rates of candidates. In the United States, the rules governing lung allocation have been modified to prioritize candidates with the most urgent need for transplantation, who would be expected to benefit the greatest from transplantation (5, 6). In Europe, different countries have adopted different approaches. Those affiliated with Eurotransplant have developed a system of priority based on predefined criteria, depending on the type of disease (7). In France, the decision was also made to prioritize allocation of donor lungs to candidates with conditions posing an immediate threat to life. This high-emergency LTx (HELTx) system was implemented in July 2007, but the consequences of these emergency/priority allocation rules have yet to be fully assessed. The rules could potentially make access to LTx more difficult for patients not fulfilling the emergency criteria.

Survival analysis is a key element in the evaluation of this new allocation strategy. Therefore, we aimed to assess the survival outcome of patients undergoing HELTx in France in the 2-year period after the initiation of the strategy.


Characteristics of Patients Before LTx

Forty-two patients were placed on the list for HELTx from July 1, 2007, to June 30, 2008, in nine centers. They represent the large majority of patients in whom a request of HELTx was addressed to the “Agence de la Biomédecine” (rate of acceptance of demands: 95% in 2007 and 98% in 2008). The characteristics of these 42 patients are given in Table 1. Ten of these patients did not receive a graft; the underlying diseases were cystic fibrosis (CF; n=6), pulmonary fibrosis (n=3), and post-LTx primary graft failure (n=1). This latter patient was placed on the HELTx list despite a theoretical contraindication for HELTx. Eight patients died while on the waiting list because their condition worsened: 7 died within 14 days of being placed on the HELTx list and the remaining patient (with pulmonary fibrosis) died because of a lack of lung availability during the maximum period of 2 weeks on the HELTx list. Two patients with CF were removed from the HELTx list because their respiratory condition improved. Thus, 32 patients (17.2% of the 186 patients who underwent LTx in the nine centers) underwent HELTx during the study period.

Characteristics of the 42 patients placed on waiting list for HELTx

HELTx accounted for 18.6%, 8%, 18.2%, and 21.7% of all LTx procedures performed during the four successive trimesters of the study. The mean age of the 32 patients undergoing HELTx was 33.4±15.9 years. The underlying diseases were CF (n=19; 59.4%), pulmonary fibrosis (n=7; 21.9%), chronic obstructive pulmonary disease (COPD; n=2; 6.3%), pulmonary hypertension (n=2; 6.3%), and other conditions (n=2; 6.3%). Among these 32 patients, 3 did not fulfill the inclusion criteria for HELTx and were placed on the list by the national college of experts; their underlying diagnoses were retransplantation (n=1) and COPD (n=2). The reasons for patients being selected for HELTx were risk of invasive mechanical ventilation (MV; n=20), invasive MV (n=8), and extracorporeal membrane oxygenation (ECMO) combined with MV (n=4).

The median time between inclusion on the LTx waiting list and inclusion on the HELTx list was 1 day (interquartile range [IQR]: 0–46.5 days). Eleven patients were registered on both lists on the same day. The median time between placement on the HELTx list and transplantation was 3 days (IQR: 1–8 days).

LTx Characteristics and Postoperative Outcome

Smoking history was present in 10 of 32 donors. The mean age of the donors was 41.5±14 years, and their mean PAO2/FIO2 ratio was 451±72. The LTx procedure was unilateral (n=9) or bilateral (n=23; Table 2). Cardiopulmonary bypass was used during surgery for 17 patients undergoing double LTx (73.9%) and 6 patients undergoing unilateral LTx (66.7%). ECMO was continued after surgery in three patients. The median duration of posttransplant MV was 9 days (IQR: 2.7–29 days). In the early postoperative period, 17 patients (53%) experienced grade III primary graft dysfunction and 13 (40.6%) acute renal failure requiring hemodialysis.

Characteristics of the 32 patients who underwent high-emergency lung transplantation

The median length of stay in the intensive care unit (ICU) after LTx for HELTx patients was 12.5 days (IQR: 12–40 days), whereas that for non-HELTx patients was 11 days (IQR: 6–23 days; P<0.01). HELTx and non-HELTx patients did not differ in median length of hospital stay: 44 days (IQR: 30.5–61.5 days) versus 36 days (IQR: 26–54 days).

The median follow-up for HELTx recipients was 514.5 days (IQR: 53–834 days). Hospital mortality rate (within 30 days of surgery) was 16%. Survival rates for the HELTx patients were 90.5%, 71%, 64.5%, 55%, and 51.5% at 1, 3, 6, 12, and 24 months, respectively. These values were significantly lower than those for the 154 patients who underwent regular, nonurgent LTx during the study period (88.5%, 83%, 79%, 77%, and 71%, respectively; P=0.03; Fig. 1). By comparison, global 1-year survival was 76.7% for all LTx procedures in France for patients transplanted from July 2006 to June 2007, that is, the year before the implementation of the new HE rules (Agence de la Biomédecine, annual report,

Posttransplant survival for the 32 high-emergency lung transplantation (HELTx) patients and for 154 non-HELTx patients.

The characteristics of the 12 patients who died after HELTx procedure are given in Table 3.

Characteristics of the 12 patients who died after HELTx procedure

Survival Outcome According to HELTx Indication

Among the 24 patients placed on the HELTx waiting list because of risk of imminent intubation, 20 eventually received a graft. The median length of stay in the ICU was 15.5 days (IQR 11.5–26.5 days), and the median length of stay in the hospital was 36.5 days (28.0–50.0 days). Survival rates were 89.7%, 73.9%, 63.3%, 47.5, and 42.2% at 1, 3, 6, 12, and 24 months, respectively.

Among the 12 patients placed on the HELTx waiting list because of requirement for invasive MV, 8 eventually received a graft. The median length of stay in the ICU was 24.0 days (IQR: 11.5–42.0 days), and the median length of stay in the hospital was 44.5 days (21.5–70.5 days). Survival rates were 87.5%, 62.5%, 62.5%, 62.5%, and 62.5% at 1, 3, 6, 12, and 24 months, respectively.

Among the six patients placed on the HELTx waiting list because of requirement for ECMO, four eventually received a graft. The median length of stay in the ICU was 43.0 days (IQR: 29.0–61.0 days), and the median length of stay in the hospital was 61.5 days (55.0–82.5 days). Survival rates were 100%, 75%, 75%, 75%, and 75% at 1, 3, 6, 12, and 24 months, respectively.


Worldwide, the number of potential candidates for LTx far exceeds the number of available lungs. As a consequence, patients often have to wait a long time for transplantation, and the mortality rate while on the waiting list is high. In France, where more than 200 LTxs are performed yearly, approximately 30 patients die each year while on the waiting list (death rate of 8.6% on waiting list in 2006 before the implementation of the new HE rules, according to the Agence de la Biomédicine, annual report, The risk of death while on the waiting list differs among patients and depends highly on the type of underlying disease. The risk is highest for patients with pulmonary fibrosis and lowest for those with emphysema (4, 8). Different countries have taken different measures to increase the number of available grafts, thus permitting a better satisfaction of the demand (promotion of organ donation from brain-dead patients, use of non-heart-beating donors, and efforts to increase the proportion of lungs procured and used). Another approach involves facilitating LTx access for patients with the highest risk of death by modifying the rules governing the allocation of lung grafts. This approach underlies the lung allocation score (1, 5, 6, 9) implemented in the United States since 2005. This score, based on medical urgency and the expected outcome after transplantation, has allowed for shortening the waiting time (10–12) and may also have contributed to the observed decrease in mortality while on the waiting list (9, 10, 13).

Another approach has been chosen by Eurotransplant, the organ exchange organization of several European countries. This organization gives priority for transplantation to patients with predefined urgency criteria. The cases are classified as being urgent or highly urgent. However, the positive or negative consequences of this approach have not been fully evaluated. Some results of this strategy have been recently reported with, in particular, a median waiting time until LTx of 52 days (7). In Spain, LTx candidates may remain eligible for urgent LTx for many years. The criteria for priority access to LTx defined by the Spanish National Transplant Organization are life-threatening pulmonary hypertension or need for invasive MV. From 1998 to 2002, 73 (10.4%) of the 697 LTxs performed in Spain were classified as “urgent” (14) and were due to MV in 82% of these patients. In most cases, the underlying diagnosis was pulmonary fibrosis, CF, or pulmonary hypertension. These patients underwent LTx after a mean waiting time of 7.7 days. Despite poor overall survival rates (47.9% and 37.1% at 1 and 5 years, respectively), which agrees with our results, the authors concluded that urgent LTx was a satisfactory option. A group from Cordoba, Spain, recently reported on the results of LTx in 78 patients with CF (15): 23 of these patients (29.5%) had undergone urgent LTx while on invasive MV. The survival rate for this group of patients was similar to that for patients who had undergone regular LTx.

Our findings concerning the consequences of the new allocation rules implemented in France since 2007, which allow for performing urgent LTx in patients with the highest short-term risk of death, are clearly preliminary but nonetheless raise several interesting questions. Our data indicate that (1) the emergency procedure based on strict criteria allows for rapid procurement of organs, with LTx performed after a median of 3 days while on the HELTx waiting list and (2) the survival results for HELTx were poorer than those for nonurgent, regular LTx, which confirms Spanish results.

Concerning the latter point, our results also confirm the data obtained in the United States by Mason et al. (16) from the United Network for Organ Sharing, demonstrating a worse posttransplant survival in patients on MV or ECMO before LTx.

The short waiting time between being placed on the HELTx list and LTx, one of the main characteristics of our approach, allows patients with the most severe disease to undergo LTx more rapidly than those with the highest lung allocation score and also the highly urgent Eurotransplant patients. This short waiting time is explained by the very strict HELTx criteria, which have been chosen to restrict the number of HELTx patients on a waiting list for LTx in France to one or two at any given moment.

Despite the poor survival results we observed, HELTx allows for survival for patients who would probably have died while on the waiting list before the implementation of these rules. The emerging possibility of access to LTx in a selected group of patients has led us to reconsider the management of pulmonary fibrosis or CF in patients who experience an episode of acute respiratory failure. Before the implementation of the new allocation rules, most of these patients were denied invasive MV in France, because the outcome was almost invariably fatal (17–19). Now that HELTx can be performed with only a short time lag between inclusion on the HELTx list and LTx, MV should not be contraindicated in these patients. However, the policy adopted at most centers is to restrict the indication for invasive MV to patients who have already been evaluated for LTx.

Some deleterious consequences of the new allocation rules should also be pointed out. One of the major consequences is probably an increase in waiting time to LTx for patients with COPD, because the total number of lung transplants performed each year in France has remained stable. As a result, patients with COPD probably eventually undergo transplantation after a longer period on the waiting list and are then in a worse general state, and death rates for these patients while on the waiting list are probably higher. Beyond the specific problem of patients with COPD, the implementation of the HELTx rules could lead to an increase in waiting list mortality when donor lungs are scarce and could promote futile transplantation, thus leading to a resource-intensive intervention that provides little benefit. Because our study did not address the effect of HELTx on waiting list outcomes, we only provide a partial description of how HELTx might benefit our patients. The annual report of the “Agence de la Biomédecine” ( indicates that the rate of patients who died on waiting list or were removed from the list for clinical deterioration has not increased from 2005 to 2010, so to date the implementation of HELTx rules has not led to deleterious consequences. However, we recommend caution because the negative consequences could be delayed.

Another anticipated effect of the new allocation rules is that given the expected increase in waiting time for those not fulfilling the HELTx criteria, a larger number of patients who would previously have undergone regular LTx will eventually “automatically” reach the criteria for HELTx. These effects will clearly be most marked if the rate of HELTx increases over time. For example, in France, where HE allocation rules have also been used for heart transplantation since 2004, the frequency of HE heart transplantation has increased, with more than 70% of all heart transplants performed each year being HE procedures. If the rates for HELTx were to reach this figure, gaining access to regular nonurgent LTx would become very difficult. However, recent data have shown that the number of cases of HELTx did not increase during the second year after the policy implementation, which reflects a natural tendency toward self-limitation among the physicians responsible for LTx.

One of main concern faced by the LTx teams is the gain of patient-years that can be achieved with a transplant program. This gain is greatest when only CF, fibrosis, and idiopathic pulmonary arterial hypertension patients are transplanted as long as they are stable with 1-year survival more than 75%, but the gain of patient-years decreases once the recipients are urgency patients with decreased posttransplant survival. Clearly, the balance between the positive and negative effects of HELTx depends on the results of the procedure, because defending the HE rules if they give poor results would be difficult. In other words, should patients undergo a strict selection process before being placed on the HELTx waiting list? More information is required before we can answer this question.

This study has several limitations. Our results remain preliminary, with only a small cohort of patients followed for a short period of time. We therefore cannot exclude the possibility of a deleterious influence of the HELTx procedure on medium-term survival. Despite these limitations, which prevent us from drawing any immediate definitive conclusions, this analysis is an essential first step toward the evaluation of HELTx, for which data are currently scarce.

In summary, our data demonstrate that the new lung allocation rules implemented in France since 2007 allow for rapid organ procurement for patients at high risk of death in the short term. The survival results for HELTx were poorer than those for regular LTx. HELTx offers the possibility of survival for patients who probably would have died while on the waiting list in the past, but some negative consequences of these new allocation rules include an increase in the difficulty of access to LTx for those not selected for the HE procedure. Therefore, more information is required before any definitive conclusions can be drawn concerning these new allocation rules.


Among the 10 centers that perform LTx in France, 9 agreed to participate in this study. We retrieved the following data related to all cases listed for HELTx in France from July 1, 2007, to June 30, 2008.

Preoperative data include age, sex, underlying diagnosis, dependence on oxygen therapy, need for invasive or noninvasive MV, duration of MV, need for ECMO, use of specific treatment (aiming to reverse the pulmonary vascular remodeling process) for pulmonary hypertension and/or inotropic agents, time between being placed on the waiting list for elective LTx and for HELTx, and time between being placed on the HELTx list and transplantation.

Perioperative data include type of procedure (single or bilateral LTx), use of cardiopulmonary bypass, or ECMO.

Postoperative data include need for further surgery, duration of MV, need for ECMO, occurrence of primary graft failure or acute renal failure, length of stay in the ICU and in the hospital, and survival after transplantation. Primary graft failure was defined according to standard criteria (20). Acute renal failure was defined as the need for hemodialysis.

Organization of HELTx in France

In France, the rules for organ allocation are developed by the French National Transplantation Agency (Agence de la Biomédecine), together with professionals working in transplantation. The agency is responsible for managing the national waiting list, coordinating organ procurement and organ allocation. Donor lungs are offered first to patients identified as having high-emergency status. In case of regular transplantation, donor lungs are proposed sequentially to transplant teams at the local, regional, and national level.

HELTx priority was established in July 2007. With the agreement of the agency, a board of experts defined, for each group of diseases, a list of criteria giving patients national priority for access to LTx.

The patients on the HELTx list are already registered on a waiting list for LTx but present a life-threatening condition because of rapid clinical deterioration. When a patient deemed suitable for LTx experience a rapid clinical deterioration during the pretransplant evaluation, transplant teams are allowed to register him subsequently on regular and HELTx lists on the same day. For inclusion on the HELTx list, the general status of the patient must remain compatible with LTx procedures, and the patient must meet the specific criteria for the initial disease (Table 4).

Criteria for inclusion on the waiting list for high-emergency lung transplantation

The procedure for adding a patient to the HELTx list is as follows. The center requesting HE priority sends to the agency an electronic form detailing the characteristics of the recipient. The form is then transferred to an expert (from a panel of LTx physicians from other centers) who checks that the request is appropriate. The expert who has to state on the HELTx demand is aware of the name of the requesting center but the transplant team does not know the identity of the expert. If the expert validates the request, the patient is given priority status, at a national level, for 7 days. At the end of this period, the HE priority period may be extended for a further 7 days. Only one request may be made for a given patient. Patients not fulfilling the criteria for HELTx remain on the waiting list for regular LTx. Improvements in the patient’s respiratory condition may result in removal from the HELTx list, but the patient remains on the waiting list for regular LTx.

The board of experts did not list COPD as a potential indication for HELTx, even in cases of invasive MV, because it was considered that even in this setting, patients were not at imminent risk of death without LTx. Retransplantation was also considered an exclusion criterion for HELTx. However, cases are considered on an individual basis, and the expert is allowed to authorize placement on the HELTx list even if the case does not meet the official HELTx inclusion criteria. The number of rejected demands has been very low (rate of acceptance of HELTx demands: 95% in 2007 and 98% in 2008).

Statistical Analysis

Data are summarized with absolute and relative frequencies for qualitative variables and mean±standard deviation or median (IQR), according to the type of distribution, for quantitative variables. We compared the characteristics of patients in the urgent and nonurgent LTx groups using Fisher’s exact test for qualitative variables and two-sample t test or Wilcoxon nonparametric tests, as appropriate, for quantitative variables. Survival was estimated by the Kaplan-Meier method. Log-rank tests were used to compare the urgent and nonurgent LTx groups. The outcome for patients who underwent HELTx was compared with that for the 154 patients who underwent non-HELTx in the same centers during the same period (underlying diseases: CF [n=52; 33.8%], pulmonary fibrosis [n=40; 26.0%], COPD [n=50; 32.5%], pulmonary hypertension [n=1; 0.7%], and other [n=11; 7.1%]). P<0.05 was considered statistically significant. Analyses involved use of Stata v10.0.


1. Orens JB, Garrity ER Jr. General overview of lung transplantation and review of organ allocation. Proc Am Thorac Soc 2009; 6: 13.
2. Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med 1999; 340: 1081.
3. Trulock EP. Lung transplantation. Am J Respir Crit Care Med 1997; 155: 789.
4. McCurry KR, Shearon TH, Edwards LB, et al.. Lung transplantation in the United States, 1998-2007. Am J Transplant 2009; 9: 942.
5. Egan TM, Murray S, Bustami RT, et al.. Development of the new lung allocation system in the United States. Am J Transplant 2006; 6: 1212.
6. Davis SQ, Garrity ER Jr. Organ allocation in lung transplant. Chest 2007; 132: 1646.
7. Smits JM, Nossent GD, de Vries E, et al.. Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant. J Heart Lung Transplant 2011; 30: 22.
8. Hosenpud JD, Bennett LE, Keck BM, et al.. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet 1998; 351: 24.
9. Hachem RR, Trulock EP. The new lung allocation system and its impact on waitlist characteristics and post-transplant outcomes. Semin Thorac Cardiovasc Surg 2008; 20: 139.
10. Kozower BD, Meyers BF, Smith MA, et al.. The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study. J Thorac Cardiovasc Surg 2008; 135: 166.
11. Iribarne A, Russo MJ, Davies RR, et al.. Despite decreased wait-list times for lung transplantation, lung allocation scores continue to increase. Chest 2009; 135: 923.
12. Levine SM, Angel LF. Is the lung allocation score working? A qualified: yes. Chest 2009; 135: 890.
13. Chen H, Shiboski SC, Golden JA, et al.. Impact of the lung allocation score on lung transplantation for pulmonary arterial hypertension. Am J Respir Crit Care Med 2009; 180: 468.
14. Román A, Calvo V, Ussetti P, et al.. Urgent lung transplantation in Spain. Transplant Proc 2005; 37: 3987.
15. Algar FJ, Moreno P, Cano JR, et al.. Urgency-code lung transplantation for cystic fibrosis: experience and results. Transplant Proc 2008; 40: 3067.
16. Mason DP, Thuita L, Nowicki ER, et al.. Should lung transplantation be performed for patients on mechanical respiratory support? The US experience. J Thorac Cardiovasc Surg 2010; 139: 765.
17. Stern JB, Mal H, Groussard O, et al.. Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure. Chest 2001; 120: 213.
18. Blivet S, Philit F, Sab JM, et al.. Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for respiratory failure. Chest 2001; 120: 209.
19. Fumeaux T, Rothmeier C, Jolliet P. Outcome of mechanical ventilation for acute respiratory failure in patients with pulmonary fibrosis. Intensive Care Med 2001; 27: 1868.
20. Christie JD, Carby M, Bag R, et al.. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2005; 24: 1454.

Lung transplantation; Prognosis; Organ allocation

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